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A Study of Antihypertensive Drugs and Depressive Symptoms (SADD-Sx) in Patients Treated With a Calcium Antagonist Versus an Atenolol Hypertension Treatment Strategy in the International Verapamil SR-Trandolapril Study (INVEST)

Ried, L Douglas PhD; Tueth, Michael J. MD; Handberg, Eileen PhD; Kupfer, Stuart MD; Pepine, Carl J. MDthe INVEST Study Group

doi: 10.1097/01.psy.0000160468.69451.7f
Original Articles

Background: The International Verapamil/Trandolapril Study (INVEST) demonstrated comparable efficacy between verapamil SR and atenolol antihypertensive treatment strategies for clinical outcomes and blood pressure (BP) control in hypertensive patients with coronary artery disease (N = 22,576). Effects of these antihypertension strategies on mood-related issues are not well understood.

Objectives: The objectives of this study were 1) to compare depressive symptoms by strategy and 2) to identify predictors of depressive symptoms in INVEST patients after 1 year of follow up.

Design, Setting, and Patients: Depressive symptoms were assessed in a subset (N = 2317) of consecutively randomized U.S. patients enrolled between April 1, 1999, and October 31, 1999. Patients were mailed surveys after randomization and after 1 year of treatment.

Intervention: Patients were assigned to either a verapamil SR or atenolol strategy to achieve Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure BP goals. Trandolapril and/or hydrochlorothiazide were recommended as add-on agents.

Main Outcome Measure: Depressive symptoms were measured by the Center for Epidemiologic Studies–Depression (CES-D) scale.

Results: CES-D scores improved 1.45 points (p < .001) after 1 year in patients assigned to the verapamil SR strategy, whereas a nonsignificant improvement was observed in patients assigned to the atenolol strategy (0.27 points, p = .44). Predictors of higher depressive symptoms were higher baseline CES-D score (p < .001), history of depression diagnosis (p = .03), history of stroke (p < .001), and assignment to the atenolol strategy (p < .001).

Conclusions: A verapamil SR strategy is a viable alternative to beta-blocker therapy for hypertensive patients with coronary artery disease, especially those at risk of depression.

CAD = coronary artery disease; MI = myocardial infarction; SADD-Sx = Study of Antihypertensive Drugs and Depressive Symptoms; INVEST = International Verapamil SR-Trandolapril Study; CES-D = Center for Epidemiologic Studies–Depression scale; JNC VI = Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

From the Rehabilitation Outcomes Research Center (L.D.R.) and the Department of Psychiatry (M.J.T.), Malcom Randall Veterans Affairs Medical Center, Department of Veterans Affairs, Gainesville, Florida; the College of Pharmacy, University of Florida, Gainesville, Florida (L.D.R.); the Department of Psychiatry (M.J.T.) and the Division of Cardiovascular Medicine, Department of Medicine (E.H., C.J.P.), College of Medicine, University of Florida, Gainesville, Florida; and Abbott Laboratories, Abbott Park, Illinois (S.K.).

Address correspondence and reprint requests to L. Douglas Ried, PhD, Pharmacy Health Care Administration, College of Pharmacy, PO Box 100496, University of Florida, Gainesville, FL 32610-0496. E-mail:

Received for publication July 21, 2004; revision received November 30, 2004.

This study was supported by Abbott Laboratories and the University of Florida.

Copyright © 2005 by American Psychosomatic Society
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